To determine if PHA-739358 has an antitumor activity against breast, ovaria, pancreatic, colerectal, small and non small cell squamous lung cancer.
ID
Source
Brief title
Condition
- Endocrine and glandular disorders NEC
- Gastrointestinal conditions NEC
- Miscellaneous and site unspecified neoplasms benign
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
• Progression Free Rate at 4 months of treatment.
Secondary outcome
Response Rate (CR / PR) according to the RECIST Criteria.
• Overall Survival.
• Duration of stabilization and duration of response.
• Ratio between the PHA-739358*s TTP and the TTP observed in the immediately
previous chemotherapy line.
• Overall Safety profile of PHA-739358 characterized by type, frequency,
severity (graded using the National Cancer Institute Common Terminology
Criteria for Adverse Events [NCI CTCAE] Version 3.0), timing and relationship
to study therapy of adverse events and laboratory abnormalities.
• Concentration of PHA-739358 in plasma at two different times: one a few
minutes before start of infusion and one a few minutes before end of infusion.
These two samples (taken at cycles 1, 2, 4 and 8) will allow to monitor the pre
and post plasma drug concentration.
• Genes/proteins which might predict responsiveness to PHA-739358 in tumor
biopsies from ovarian cancer patients.
• Genes/proteins which might predict responsiveness to PHA-739358 in tumor
biopsies from NSCLC patients with squamous cell histology.
Background summary
Histology has recently emerged as a potential predictive factor fors ome
compounds in the treatment of advanced non-small cell lung cancer (NSLC).
After analyses of the data obtained from the AURA-6202-006 study in different
patient populations, classified according to the tumor histology, revealed that
the group of patients with non-squamous tumor had a median PFS (95% CI) of 6,4
months (4.2-10.2) and a median OS (95%CI) of 10.6 months (10.3-). These values
are in fact better than those reported in the literature for patients with the
same histology treated with the standard docetaxel chemotherapy (PFS= 2.7
months, OS=7.4 months) This evidence of activity of PHA-739358 in the treatment
of squamous NSCLC is based on data obtained of 7 patients, thus requiring more
information.
Therefore, the main purpose of this protocol amendment are the following:
- to expand the investigation in the squamous NSCLC patient group.
- To characterize some basal squamous cell carcinoma molecular features related
to the mechanisme of action of PHA-739358 and to identify potential biomarkers.
- To add a peer-review of all CT scans of this group patients.
Study objective
To determine if PHA-739358 has an antitumor activity against breast, ovaria,
pancreatic, colerectal, small and non small cell squamous lung cancer.
Study design
Adult patients, with histologically or cytologically confirmed diagnosis of
progressive advanced/metastatic breast, ovarian, colorectal, pancreatic, small
cell lung or non small cell lung cancers, will receive PHA-739358 by a 24-hour
IV infusion every 14 days at the dose of 500 mg/m2 until study completion,
disease progression, patient refusal, patient withdrawal of consent, patient
change in medical status, non-compliance by patient with protocol requirements,
unacceptable toxicity, whichever comes first.
Intervention
PHA-739358 will be dosed based on the patients bsa. This will be 500 mg/m2 by
24 hours IV infusion on day 1 in a 14 day cycle, in absence of a grade 3 or
higher hematological toxicity the dose can be increased to 580 mg/m2 in the
second cycle.
Study burden and risks
Patients will undergo a full medical examination. An elctrocardiogram (ECG) and
a scan (MUGA) or cardiac echograpy to monitor the hartfunction, a laboratory
blood test, and radiographs, CT scan or Magnetic Resonance Imaging (MRI) to
assess the extent of the tumor.
A pregnancy test for women of childbearing capacity will be performed.
All patients having chemotherapy will need to have frequently blood samples
taken, and there is a risk of bruising or pain, at the site from where the
blood was drawn.
Cardiac function will be monitored at regular intervals with MUGA scan or
echocardiography.
Viale Pasteur, 10
20014 Nerviano (Mil)
IT
Viale Pasteur, 10
20014 Nerviano (Mil)
IT
Listed location countries
Age
Inclusion criteria
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:
1. Patients with histologically or cytologically documented progressive advanced/metastatic disease in one of the following solid tumors (see below):
• Breast cancer (in 3rd line of chemotherapy),
• Ovarian cancer (3rd line, platinum resistant/refractory disease),
• Colorectal cancer (3rd line),
• Pancreatic Cancer (2nd line),
• Small Cell Lung Cancer (2nd line),
• Non Small Cell Lung Cancer (2nd line),
• Squamous Non Small Cell Lung cancer (2nd line).;Note: Any adjuvant chemotherapy followed by the recurrence of the disease within 12 months after the start of the adjuvant treatment will be considered as one chemotherapy line for advanced/metastatic disease.
Platinum Resistant: Disease that relapsed within 6 months after completing prior platinum therapy
Platinum Refractory: Disease that progressed or was stable during prior platinum therapy
2. Prior chemotherapy must have been completed 2 weeks before study entry.
3. Available information on the first day of administration of the previous chemotherapy and the precise date when progression has been assessed.
4. Prior radiotherapy is allowed provided that a minimum of 2 weeks has elapsed between the end of prior radiotherapy and the entry into the trial.
5. Age 18 years or older
6. ECOG performance status 0 - 1
7. Life expectancy of at least 3 months
8. Hematological and biochemical parameters:
• Bilirubin <=1,5 UNL
• AST/ALT <= 2,5 UNL (<= 5 UNL in case of liver metastases)
• ALP <= 2,5 UNL (<= 5 UNL in case of liver and/or bone metastases)
• Creatinine within normal limits (if out of range then perform the Creatinine clearance evaluation >= 50 ml/min).
• ANC >= 1,500 cells/mm3
• Platelets count >= 75,000 cells/mm3
• Hemoglobin >= 10 g/dl
9. All acute toxic effects (excluding alopecia) of any prior therapy must have resolved to NCI CTCAE version 3.0 grade <= 1
10. Personally signed and dated IEC/IRB-approved informed consent form
11. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
Exclusion criteria
The presence of any of the following will exclude a subject from study enrollment:
1. Previous high-dose chemotherapy requiring bone marrow rescue.
2. Concurrent enrollment in another investigational drug trial within the last 4 weeks
3. Known brain or leptomeningeal disease (baseline computerized tomography [CT] or MRI scan of the brain required only in case of clinical suspicion of central nervous system metastases)
4. Uncontrolled hypertension with blood pressure exceeding 160/100 mmHg
5. Pregnancy or breast-feeding. Female patients must agree to avoid becoming pregnant during the study and in the following 3 months after the end of the treatment, be surgically sterile or be postmenopausal. Male patients must agree to have no intention to father a child during the study and in the following 3 months after the end of the treatment.
6. Abnormal LVEF < 40% by Echocardiography or MUGA <45%
7. Any of the following in the past 6 months: myocardial infarction, unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis or other significant thromboembolic event
8. Cardiac dysrhythmias grade * 2 according to NCI CTCAE version 3.0
9. Known active infection including known human immunodeficiency virus (HIV) positivity
10. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for entry into this study.
11. History of previous cancer, except skin basal-cell carcinoma or in situ carcinoma of the cervix, within the previous 5 years.
12. Marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval > 450 milliseconds (ms))
13. A history of additional risk factors for torsade de pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)
14. Use of concomitant medications that prolong the QT/QTc interval.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2006-003772-35-NL |
| CCMO | NL16674.078.07 |